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Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.

ABSTRACT: Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum. We found that TRPC1/3/5/6, TRPV1-4, TRPM8, TRPA1, TWIK2, TRAAK, TREK1, and TASK1/2 were all present in rat nodose ganglia. Both lesion results and single-cell PCR results suggested that TRPA1 and TRPC1 were preferentially expressed in neurons that were either capsaicin sensitive or TRPV1 positive. Expression of TRPM8 varied dynamically after various manipulations, which perhaps explains the disparate results obtained by different investigators. Last, we also examined ion channel distribution with the A-type CCK receptor (CCK-R(A)) and found there was a significant preference for neurons that express TRAAK to also express CCK-R(A), especially in gut-innervating neurons. These findings, combined with findings from prior studies, demonstrated that background conductances such as TRPC1, TRPA1, and TRAAK are indeed differentially distributed in the nodose ganglia, and not only do they segregate with specific markers, but the degree of overlap is also dependent on the innervation target.

SUBMITTER: Zhao H

PROVIDER: S-EPMC2822499 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.

Zhao Huan H Sprunger Leslie K LK Simasko Steven M SM

American journal of physiology. Gastrointestinal and liver physiology 20091203 2

Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to ...[more]

PMID: 19959819

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Project description:Constitutively active background or "leak" two-pore-domain potassium (K(+)) channels (Kcnk family), as defined by lack of voltage and time dependency are central to electrical excitability of cells by controlling resting membrane potential and membrane resistance. Inhibition of these channels by several neurotransmitters, e.g. glutamate, or acetylcholine, induces membrane depolarization and subsequent action potential firing as well as increases membrane resistance amplifying responses to synaptic inputs. In contrast, their opening contributes to hyperpolarization. Because of their central role in determining cellular excitability and response to synaptic stimulation, these channels likely play a role in the differential effects of vestibular efferent neurons on afferent discharge. Microarray data from previous experiments showed Kcnk 1, 2, 3, 6, 12 and 1 5 mRNA in Scarpa's ganglia. Real-time RT-PCR showed Kcnk 1, 2, 3, 6, 12 and 15 mRNA expression in Scarpa's ganglia and Kcnk 1, 2, 3, 6, 12 but not 15 mRNA expression in the crista ampullaris. We studied the distribution of two-pore-domain potassium channels K(2P)1.1, 2.1, 3.1 and 6.1 like immunoreactivity (corresponding to Kcnk genes 1, 2, 3 and 6) in the vestibular periphery. K(2P)1.1 (TWIK 1) immunoreactivity was detected along nerve terminals, supporting cells and blood vessels of the crista ampullaris and in the cytoplasm of neurons of the Scarpa's ganglia. K(2P)2.1 (TREK 1) immunoreactivity was detected in nerve terminals and transitional cells of the crista ampullaris, in the vestibular dark cells and in neuronal fibers and somata of neurons of Scarpa's ganglia. K(2P)3.1 (TASK 1) immunoreactivity was detected in supporting cells and transitional cells of the crista ampullaris, in vestibular dark cells and in neuron cytoplasm within Scarpa's ganglia. K(2P)6.1 (TWIK 2) immunoreactivity was detected in nerve terminals, blood vessels hair cells and transitional cells of the crista ampullaris and in the somata and neuron fibers of Scarpa's ganglia.

Project description:The KV 1/D-type potassium current (ID ) is an important determinant of neuronal excitability. This study explored whether and how ID channels regulate the activation of bronchopulmonary vagal afferent nerves. The single-neuron RT-PCR assay revealed that nearly all mouse bronchopulmonary nodose neurons expressed the transcripts of α-dendrotoxin (α-DTX)-sensitive, ID channel-forming KV 1.1, KV 1.2 and/or KV 1.6 α-subunits, with the expression of KV 1.6 being most prevalent. Patch-clamp recordings showed that ID , defined as the α-DTX-sensitive K+ current, activated at voltages slightly more negative than the resting membrane potential in lung-specific nodose neurons and displayed little inactivation at subthreshold voltages. Inhibition of ID channels by α-DTX depolarized the lung-specific nodose neurons and caused an increase in input resistance, decrease in rheobase, as well as increase in action potential number and firing frequency in response to suprathreshold current steps. Application of α-DTX to the lungs via trachea in the mouse ex vivo vagally innervated trachea-lungs preparation led to action potential discharges in nearly half of bronchopulmonary nodose afferent nerve fibres, including nodose C-fibres, as detected by the two-photon microscopic Ca2+ imaging technique and extracellular electrophysiological recordings. In conclusion, ID channels act as a critical brake on the activation of bronchopulmonary vagal afferent nerves by stabilizing the membrane potential, counterbalancing the subthreshold depolarization and promoting the adaptation of action potential firings. Down-regulation of ID channels, as occurs in various inflammatory diseases, may contribute to the enhanced C-fibre activity in airway diseases that are associated with excessive coughing, dyspnoea, and reflex bronchospasm and secretions. KEY POINTS: The α-dendrotoxin (α-DTX)-sensitive D-type K+ current (ID ) is an important determinant of neuronal excitability. Nearly all bronchopulmonary nodose afferent neurons in the mouse express ID and the transcripts of α-DTX-sensitive, ID channel-forming KV 1.1, KV 1.2 and/or KV 1.6 α-subunits. Inhibition of ID channels by α-DTX depolarizes the bronchopulmonary nodose neurons, reduces the minimal depolarizing current needed to evoke an action potential (AP) and increases AP number and AP firing frequency in response to suprathreshold stimulations. Application of α-DTX to the lungs ex vivo elicits AP discharges in about half of bronchopulmonary nodose C-fibre terminals. Our novel finding that ID channels act as a critical brake on the activation of bronchopulmonary vagal afferent nerves suggests that their down-regulation, as occurs in various inflammatory diseases, may contribute to the enhanced C-fibre activity in airway inflammation associated with excessive respiratory symptoms.

Dataset Information

Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.

Publications

Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.

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